Focused therapies and immunotherapies provide new remedy choices for extra sorts of most cancers, however these medication are much less useful when tumors produce a number of copies of a gene. This gene amplification contributes to drug resistance. Boundless Bio’s analysis into what drives this phenomenon has yielded new understanding of most cancers biology. The corporate now has $100 million in IPO money to assist two packages in early medical improvement and extra in its pipeline.
Boundless Bio late Wednesday priced its providing of 6.25 million shares at $16 every, which was the midpoint of the preliminary $15 to $17 value vary the San Diego-based firm set final week. These shares will commerce on the Nasdaq underneath the inventory image “BOLD.”
The analysis of Boundless Bio focuses on extrachromosomal DNA, or ecDNA. These circle-shaped models of DNA aren’t current in wholesome cells however they’re discovered floating inside some most cancers cells, the place they’re a major driver of gene amplification, the corporate mentioned in its IPO submitting. The ecDNA permits resistance to a focused remedy by switching amplification to a special gene that’s not focused by the drug. Amplification of a mutant cancer-driving gene may also spark resistance to therapies concentrating on that mutation. However ecDNA-enabled resistance shouldn’t be restricted to focused therapies. It could actually additionally allow resistance to chemotherapy, the corporate mentioned within the submitting.
Moderately than concentrating on proteins produced by amplified oncogenes the way in which that focused most cancers therapies do, Boundless Bio goals to intrude with a most cancers cell’s capacity to make use of ecDNA. Boundless Bio’s proprietary platform know-how, Spyglass, identifies druggable targets which might be important to ecDNA formation and performance. The corporate hits these targets with ecDNA-directed therapeutic candidates, or ecDtx for brief. These small molecules work by exploiting mobile vulnerabilities of ecDNA-enabled cancers.
“Accordingly, our ecDTx are designed to preferentially kill ecDNA-bearing most cancers cells, however not wholesome cells with out ecDNA,” Boundless Bio mentioned within the submitting. “They’re engineered to disrupt the underlying mobile equipment that permits ecDNA to operate correctly, similar to proteins important for ecDNA replication, transcription, meeting, restore, and segregation.”
Boundless Bio’s lead drug candidate, BBI-355, targets checkpoint kinase 1 (CHK1), an enzyme that manages ecDNA replication and transcription in most cancers cells. There are not any FDA-approved CHK1 inhibitors, however Acrivon Therapeutics is in Section 2 testing with a CHK1 and CHK2 inhibitor licensed from Eli Lilly. That drug is run intravenously. Boundless Bio’s CHK1 inhibitor is an oral drug. A Section 1/2 check is underway in sufferers with oncogene-amplified cancers and preliminary proof-of-concept knowledge are anticipated within the second half of this 12 months. Preclinical knowledge will likely be introduced subsequent week in the course of the American Affiliation for Most cancers Analysis annual assembly in San Diego.
A second program, BBI-825, is designed to dam ribonucleotide reductase (RNR), an enzyme that Boundless Bio says is important for ecDNA meeting and restore in most cancers cells. Final month, the corporate started a Section 1/2 check of this drug; preliminary knowledge are anticipated within the second half of 2025. A 3rd Boundless Bio program targets a beforehand undrugged kinesin protein that the corporate says is important for ecDNA throughout cell division. An investigational new drug software is anticipated within the first half of 2026.
Gene amplification has been noticed in additional than 14% of most cancers sufferers, in line with Boundless Bio. The corporate has developed a diagnostic to establish sufferers amenable to remedy with an ecDNA-directed drug. Within the IPO submitting, the corporate mentioned it’s working with an in vitro diagnostic firm to develop this check right into a medical trial assay for the lead program’s medical trial.
Boundless Bio’s method relies on the analysis of scientific founder Paul Mischel, who’s now a Stanford College pathology professor. The corporate was based in 2018 by Arch Enterprise Companions and is led by CEO Zach Hornby, a former govt at Ignyta, a most cancers drug developer that was acquired by Roche in 2017. Mischel is chairman of Boundless Bio’s scientific advisory board.
Previous to the IPO, Boundless Bio had raised $252.1 million, in line with the submitting. The latest financing was a $100 million Collection C spherical final Could co-led by Leaps by Bayer and RA Capital Administration. The submitting exhibits that Arch is Boundless Bio’s largest shareholder with an 11.2% post-IPO stake, adopted by the ten.6% of the corporate owned by Constancy and the 8.4% owned by RA Capital. Bayer’s post-IPO stake is 6.6%.
As of the tip of 2023, Boundless Bio reported having $120.7 million in money, money equivalents, and short-term investments. The corporate mentioned within the submitting that it plans to use $22 million of the IPO proceeds towards the medical improvement of lead program BBI-355. One other $29 million is budgeted for the event of BBI-825. Boundless Bio plans to spend $24 million on the R&D of different ecDNA-directed drug candidates, together with the development of a 3rd program into human testing. The brand new capital will even assist ongoing work on the diagnostic check and the Spyglass platform.
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